IE is a potentially lethal infection requiring prolonged courses of antibiotic therapy. Currently, no consensus exists regarding duration of post-surgical antibiotics among patients undergoing surgical valve replacement for IE treatment. Although the American Heart Association (AHA) guidelines suggest up to 6 weeks of parenteral antibiotics following surgery, this recommendation is based on judgment rather than published evidence. By contrast, considerable evidence published subsequent to those guidelines now exists to suggest that 2 weeks of antibiotic therapy following valve surgery is as effective as longer courses of therapy, particularly when the tissue cultures taken from the valve at the time of surgery show no growth of the causative pathogen. A reduction in antibiotic use provides several potential advantages to the individual patient, including reductions in intravascular catheter and antibiotic-related complications, selection of resistant bacterial isolates, and costs related to extended courses of parenteral antibiotic therapy. In the current proposal we will design a multi- center, randomized clinical trial of patients who have undergone surgery for IE who will be randomized to usual treatment consisting of 6 weeks of antibiotic therapy versus a shortened 2 week course of antibiotic therapy. The primary outcome will be cure (absence of death or IE relapse) at 12 months; the secondary outcome will be adverse events related to antibiotic use and the use of intravascular catheters. The Specific Aims of the current proposal are to (1) develop the protocol and implementation tools for the clinical trial, and (2) recruit sies for participation in the clinical trial. We will accomplish these aims by leveraging the unique resources of the Duke Clinical Research Institute (DCRI), the world's largest academic clinical research organization and the International Collaboration on Endocarditis (ICE), a multinational network of investigators focused on research in IE. The overall goal of the proposed clinical trial is to demonstrate that the duration of antibiotic therapy can be reduced while maintaining effective treatment of IE. The results of this clinical trial will allow clinicians to make evidenc-based decisions regarding the duration of antibiotic therapy and will potentially reduce unnecessary antibiotic usage. PUBLIC HEALTH RELEVANCE: The overall goal of this study is to reduce antibiotic usage while maintaining effectiveness in treating IE. A shorter duration of antibiotic therapy for IE would impact patients on an individual level by potentially reducing antibiotic-related adverse events and reducing complications related to the intravascular catheters that are used to deliver parenteral antibiotics. From a societal perspective, a reduction in antibiotic usage has the potential to decrease selection of resistant bacterial isolates and to reduce costs related to prolonged intravenous antibiotic therapy.